Interleukin-2 and interferon-gamma double knockout mice reject heterotopiccardiac allografts

Background. Several studies suggest that MHC-mismatched allografts reject w ith a Th1 or Th2 immune response, but these models all have low-level expre ssion of the Th1 cytokines interleukin (IL)-2 and interferon-gamma (IFN-gam ma). Methods. We interbred mice with single targeted gene disruptions for IL-2 a nd IFN-gamma to establish IL-2 + IFN-gamma double knockout (DKO) mice. Hete rotopic cardiac allografts from DBA/2j (H2(d)) donors were transplanted WT, IL-2 knockout (KO), IFN-gamma KO, and DKO recipients (C57BL/6x129; H2(b)). Cytokine transcripts from allografts and DKO splenocytes were analyzed by reverse transcription polymerase chain reaction. Results. DKO mice had a cytokine profile and IgG1/IgG2a isotype ratio chara cteristic of Th2 deviation. DKO recipients rejected heterotopic cardiac all ografts faster than IL-2 KO mice, but significantly slower than WT and IFN- gamma RO mice (P < 0.01). Analysis of the rejecting DKO recipients showed i ntragraft Th2 cytokine expression. Conclusion. The combined absence of IL-2 and IFN-<gamma> in the setting of Th2 deviation does not prevent allograft rejection.